PHYSICAL ACTIVITY - ParkinsonNet

promotion of

physical activity

in parkinson's disease THE CHALLENGE TO CHANGE BEHAVIOR

MARLIES VAN NIMWEGEN

PROMOTION OF PHYSICAL ACTIVITY IN PARKINSON'S DISEASE the challenge to change behavior

Proefschrift ter verkrijging van de graad van doctor

The research presented in this thesis was supported by and carried out at the department of Neurology of the Nijmegen Centre of Evidence Based Practice of the Radboud University Nijmegen Medical Centre.



aan de Radboud Universiteit Nijmegen op gezag van de rector magnificus prof. mr. S.C.J.J Kortmann,

The research was further supported by grants from the Netherlands Organization for Health Research and

volgens besluit van het college van decanen

Development (ZonMw), the Michael J Fox Foundation for Parkinson’s research. Additional (financial) support

in het openbaar te verdedigen op woensdag 6 maart 2013

was provided by VGZ (health insurance company); Glaxo Smith Kline; Philips Consumer Lifestyle (DirectLife); and

om 13.30 uur precies

National Parkinson Foundation.



Printing and dissemination of this thesis was financially supported by the Radboud University Nijmegen Medical Centre, Novartis Pharma BV, Stichting Alkemade-Keuls, UCB Pharma BV, Stichting GlaxoSmithKline BV, Parkinson Vereniging, Ipsen Farmaceutica BV.



Promotion of physical activity in Parkinson’s disease feasibility and effectiveness Thesis,



Radboud University Nijmegen, the Netherlands

Design: IS=Ontwerp • Ilse Schrauwers • www.isontwerp.nl

Cover concept and movement-illustrations: Nynke Hester Bakker

Printing: Ipskamp Drukkers B.V. • www.ipskampdrukkers.nl

ISBN: 978-94-6191-598-6



© Marlies van Nimwegen



No part of this thesis may be reproduced or transmitted in any form or by any means,electronic or mechanical,

door

including photocopy, recording or otherwise without permission of the author.

Maria Louise van Nimwegen geboren op 29 januari 1982 te Apeldoorn

PROMOTOREN

Prof. dr. B.R. Bloem



Prof. dr. G.F. Borm

COPROMOTOREN

Dr. M. Munneke



Dr. S. Overeem There are two primary choices in life;

MANUSCRIPTCOMMISSIE

Prof. dr. R. Nijhuis-van der Sanden (voorzitter)



Prof. dr. J.J. van Hilten (LUMC)



Prof. dr. M. Hopman-Rock (VUmc)

to accept conditions as they exist, or accept the responsibility for changing them. Denis Waitley

promotion of physical activity in parkinson's disease • the challenge to change behavior

contents

CONTENTS CHAPTER 01

PAGE 09

INTRODUCTION & AIMS OF THIS THESIS

CHAPTER 02

A MULTIFACETED INTERVENTION AIMED TO PROMOTE PHYSICAL PAGE 19

CHAPTER 08 PAGE 33

DESIGN AND BASELINE CHARACTERISTICS OF THE PARKFIT STUDY, OF A MULTIFACETED BEHAVIORAL PROGRAM TO INCREASE PHYSICAL

PAGE 111

GENERAL DISCUSSION & FUTURE PERSPECTIVES

ACTIVITY IN PARKINSON PATIENTS

CHAPTER 10

BMC Neurology – 2010; 10:70

PAGE 123

NEDERLANDSE SAMENVATTING PAGE 49

MULTIVARIABLE ANALYSES OFTEN HAVE MULTIPLE SOLUTIONS, ALL OF WHICH SHOULD BE REPORTED

CHAPTER 11

PAGE 131

DANKWOORD

Submitted

CHAPTER 12

PAGE 137

PAGE 59

12.1 REFERENCES 12.2 LIST OF PUBLICATIONS 12.3 CURRICULUM VITAE 12.4 DISSERTATIONS OF THE PARKINSON CENTRE NIJMEGEN (PARC)

QUANTIFYING DAILY PHYSICAL ACTIVITY AND ITS DETERMINANTS IN SELF-REPORTED SEDENTARY PARKINSON’S DISEASE PATIENTS Submitted

CHAPTER 06

PAGE 103

SUMMARY

CHAPTER 09

A RANDOMIZED CONTROLLED TRIAL EVALUATING THE EFFECTIVENESS

CHAPTER 05

ACTIVITY IN PATIENTS WITH PARKINSON’S DISEASE Submitted

Journal of Neurology – 2011; 258 (12), 2214-21

CHAPTER 04

PAGE 89

EVALUATION OF IMPLEMENTATION OF THE PARKFIT PROGRAM:

PHYSICAL INACTIVITY IN PARKINSON’S DISEASE

CHAPTER 03

CHAPTER 07

PAGE 139 PAGE 157 PAGE 159 PAGE 161

PAGE 73

PROMOTION OF PHYSICAL ACTIVITY AND FITNESS IN SEDENTARY PATIENTS WITH PARKINSON’S DISEASE, A RANDOMIZED CONTROLLED TRIAL British Medical Journal – 2012; in press

6

7

CHAPTER

01

GENERAL INTRODUCTION & AIMS OF THIS THESIS

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promotion of physical activity in parkinson's disease • the challenge to change behavior

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introduction & aims of this thesis

PARKINSON’S DISEASE

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. The prevalence is estimated at around 1.3% to 1.5% for people above the age of 60 years.1 Ageing is a major risk factor for PD; due to the growing elderly population, the prevalence will increase sharply in the next decades.



PD is characterized by motor symptoms including bradykinesia, tremor, rigidity, gait disturbances and postural instability.2 In addition to these symptoms, a wide variety of non-motor symptoms like depression or apathy is present in almost all patients; examples include autonomic dysfunction, depression, fatigue, cognitive decline, and sleep disturbances.3 All these symptoms markedly impair the quality of life, and with disease progression, most patients experience severe disability. People with PD carry a relatively heavy illness burden compared with those suffering from other chronic conditions: only people with high spinal cord injury (among the conditions leading to physical impairments) and people with depression (among the conditions leading to mental impairments) scored lower on quality of life.4



The underlying causes of PD are still largely unknown, but the changes in the brain and resulting pathophysiology are becoming quite clear. It is widely appreciated that dopaminergic neurons from the pars compacta of the substantia nigra degenerate progressively, resulting in a mounting central dopamine deficiency in various dopaminergic circuitries. Levodopa, combined with a peripheral dopa decarboxylase inhibitor (benserazide or carbidopa), can correct this dopamine deficiency and remains to date the most effective therapy.5 An increasing number of other dopaminergic drugs is also available to alleviate the symptoms of PD. For a selected subgroup of patients, deep brain surgery is a therapeutic option.



As the disease progresses, non-dopaminergic brain areas become progressively involved in the neurodegenerative process. This leads to emergence of debilitating symptoms and signs that fail to respond adequately to dopamine replacement therapy or deep brain surgery. In addition to the medical management approaches, allied health interventions and specialized Parkinson nurses are increasingly deployed to treat both the dopaminergic and non-dopaminergic symptoms of PD. The evidence to support the merits of these interventions is gradually growing and treatment guidelines (partially based on evidence, partially on practical clinical experience) for some of these allied healthcare interventions have been developed6-8: for example, the use of physiotherapy is described in Textbox 1. Integrating all various treatment options into a bundled multidisciplinary approach (along with pharmacological and surgical treatment) is widely felt to represent an optimal therapeutic strategy for this complex, multifaceted disease.9 10

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promotion of physical activity in parkinson's disease • the challenge to change behavior

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introduction & aims of this thesis

PHYSICAL ACTIVITY AS A MEDICINE?

TEXTBOX 1

Although medical treatment with levodopa substantially improves the quality of life and func-

PHYSIOTHERAPY IN PD*

tional capacity, PD remains an incurable disease that results in considerable and progressive Even with optimal medical treatment, patients with PD experience a decline of body function and mobility. This can

disability for almost all affected patients. Therefore, new and better treatment approaches are

lead to inactivity and social isolation, resulting in a reduced quality of life. To reduce these motor impairments,

needed to suppress the symptoms and signs of PD, and to perhaps slow down or even arrest the

physiotherapy can be effective. The evidence-based guideline for physiotherapy in PD describes specific treatment

otherwise relentless disease progression. This thesis examines whether promotion of physical

areas.11 The objective of physiotherapy is to improve the patient’s independence, safety and well-being.

activities could represent such an intervention.

In the Netherlands, specialized physiotherapy for patients with PD - as well as other healthcare professions such

There are several reasons to assume why more physical activity might be beneficial for PD pa-

as speech & language therapy or occupational therapy - is available in regional professional networks, known as

tients. First, physical activity could have potential disease-specific effects, for example by impro-

11

Each ParkinsonNet network consists of a small number of healthcare professionals who have

ving cognitive dysfunction and mood.22-24 Second, recent studies have shown that exercise can

been specifically trained to treat PD patients according to evidence-based recommendations. To further improve

have a beneficial effect on the neurodegenerative process in rodent models of PD. Specifically,

the quality of care, ParkinsonNet aims to improve the accuracy of referrals by neurologists, and to increase the

studies in rats and mice with experimental parkinsonism indicate that exercise can prevent and

patient volume per therapist. Moreover, collaboration and communication between the participating health pro-

decelerate the development of experimental parkinsonism through several mechanisms that

fessionals is stimulated.12 A large cluster-controlled trial has shown that the ParkinsonNet concept achieves these

involve neural plasticity of the dopaminergic and glutamatergic system.25-28 Of course, extrapo-

12 13

ParkinsonNet.

13

goals, and also leads to a substantial cost reduction that may be as high as 1400 Euros per patient per year.

lation of these experimental findings to patients requires extreme caution. However, the results have fuelled speculation that exercise might perhaps be used to modify the course of PD by acting directly on the neurodegenerative process. Taken together, these symptomatic and presumed disease-modifying effects raise hope that exercise could be used as a ‘medicine’ in patients

BENEFITS OF PHYSICAL ACTIVITY

with PD. Exercise as a medicine, it sounds both easy and simple, but it is not, as we shall see in

Living an active lifestyle promotes health. The benefits of regular physical activity are extensive

14-16

: being physically active increases survival,

17 18

this thesis.

and it prevents people from chronic disea-

ses such as cardiovascular disease, diabetes, cancer, hypertension, obesity, depression and

Sedentary behavior is a major public health problem and it is one of the highest risk factors

osteoporosis. Moreover, physical activity may improve specific symptoms such as sleep impair-

for death in developed countries.29 Changing a sedentary lifestyle is difficult, even for healthy

14

ment, depression, and constipation. Several biological mechanisms may be responsible for the

people; and to increase physical activity in old persons or in patients with one or multiple chro-

benefits associated with physical activity: for example, habitual physical activity has been shown

nic conditions is even harder. This is particularly true for PD patients who typically experience

to improve vascular function and cholesterol levels, to reduce blood pressure and body weight,

a combination of both physical limitations and mental changes, which creates considerable

to prevent bone loss associated with aging, and to increase cardiac function. Because of the

barriers to become physically active. A critical question that is addressed in this thesis is whether

benefits associated with physical activity and exercise, international guidelines state that every

people with PD can achieve an enduring increase in their physical activities in daily life. And

adult “should accumulate 30 minutes or more of moderate-intensity physical activity on most,

even when such a sustained change in lifestyle is possible, it needs to be demonstrated whether

preferably all, days of the week’’.20 21 There are no reasons to assume that similar health benefits

this change can improve disease-specific symptoms and prevent development of co-morbid

will not apply to chronic patients as well.

complications.

19

* In the Netherlands, the content of the evidence-based guideline for physiotherapy in PD is identical to the guidelines for Cesar exercise therapists and Mensendieck exercise therapists. Therefore, the term ‘physiotherapy’ also includes Cesar and Mensendieck exercise therapies.

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promotion of physical activity in parkinson's disease • the challenge to change behavior

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introduction & aims of this thesis

ACHIEVING A BEHAVIORAL CHANGE; A CHALLENGE

such hazardous activities, and as such greater mobility may paradoxically increase the risk of



Despite the seemingly well-known health benefits of physical activity, almost half of the Dutch

falls. In contrast, fall risks are presumably minimal for patients who are sitting on a chair all day,

adults do not meet the international guidelines for healthy physical activity. Why is it so difficult

although one might argue that because of de-conditioning, particularly these patients are sus-

to live an active life? Why is it easier to chose the alternative – physically inactive – option? Why

ceptible to fall once they do need to make a transfer or walk. Whether or not promoting physical

is simply informing people about the potential health benefits of physical activity not enough

activities leads to more or fewer falls really needs to be tested.

to attain a sustained behavioral change? Everything that people can do for themselves is often more important than what conventional medical management can offer, but even this fact is for many people not enough to change their unhealthy lifestyle. Apparently, making healthy chan-

AIMS OF THIS THESIS

ges is easier said than done. Even when people are strongly motivated, adopting a new, healthy



habit – and even more importantly, breaking an old one – proves very difficult.

Physical activity levels of patients with PD are still unclear, and so are their determinants. Consequently, a disease-specific intervention program considering the complexity of PD and their physical activity behavior is lacking. This thesis is dedicated to the relationship between



Considerable research has been aimed at identifying factors and tools for clinicians that con-

PD and physical activity behavior, and aims to clarify some uncertainties about physical

tribute to a successful lifestyle change.30-32 As a first step, knowledge about the health risks and

activity in PD.

benefits of the specific behavior is vital: if people lack knowledge about how their habits affect their health, they have little reason to change these habits at all.33 Furthermore, according to

In Chapter 2, we examine the level of physical activity in patients with PD. Patients with PD are

social cognitive theories, behavior is based on two types of expectations: (1) self efficacy ex-

likely to become physically inactive, because of their motor, mental and emotional problems.

pectations, which are the individuals’ beliefs in their capabilities to perform a course of action

However, specific studies on the actual volume of physical activity in PD are scarce, and the

to attain a desired outcome; and (2) outcome expectations, which are the beliefs that a certain

available results are conflicting. In this chapter, we quantify daily physical activities in PD pa-

consequence will be produced by personal action. The stronger someone believes both in his

tients, and analyze the associated determinants.

33

or her abilities and the positive outcomes of the behavior, the more likely it is that he or she will change the unhealthy behavior. The transtheoretical model (TTM) has been used to understand



Since there is a lack of specific interventions that accommodate the complexity of PD and the

the stages that people progress through when they change behavior.34 The model assumes

physical activity behavior of PD patients, we developed such a PD-specific program (the ParkFit

that individuals move through different stages: precontemplation; contemplation; preparation;

program). The ParkFit program is a physiotherapy intervention that aims to increase physical

action; and maintenance. The TTM shows that behavioral change does not occur in a linear

activity levels over a period of two years in sedentary patients with PD. The intervention is based

manner and that it is a dynamic process.

on models of behavioral change, 33 34 and contains different behavioral change techniques.35 38 41



To evaluate its effectiveness, we designed a multicentre, randomized controlled trial com-

When trying to achieve an enduring behavioral change, both knowledge about this behavioral

paring ParkFit with a matched general physiotherapy intervention.42 Primary endpoint for this

change process and specific strategies such as goal setting, problem-solving techniques and

ParkFit trial was the time spent on physical activity per week. The ParkFit program as well as the

motivational interviewing is needed.33-35 Physical activity promoting programs including such

design of the trial are described in Chapter 3.

elements were effective in sedentary people36 37, in patients with chronic heart failure35, and in patients with COPD.38



Multivariable selection methods are frequently used to determine factors associated with an outcome, for example in Chapter 2 when analyzing determinants of physical activity in PD.



Although an active lifestyle has extensive benefits, an increased risk for falls is a potential other

However, it is well known that different studies often lead to different models. By using the data

side of the same coin. This concern is especially true for people with PD who have a much higher

described in Chapter 2, we show in Chapter 4 that these conflicting results are partly due to

risk of falling compared to age matched controls.

the fact that the final model is usually not unique.

39

One of the most common causes of falls

in PD appears to be freezing of gait40; other falls may result from insecure transfers or changes in posture, or when performing more than one activity at the same time.39 Promoting physical activity inevitably increases the number of daily circumstances when patients are engaged in

14



The ParkFit study intended to include sedentary patients, based on a physical activity screening questionnaire. It was uncertain whether these self-reported sedentary patients could also be

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promotion of physical activity in parkinson's disease • the challenge to change behavior

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introduction & aims of this thesis

identified as being sedentary when tested objectively for daily physical activity using quantitative ambulatory accelerometry. In Chapter 5, we therefore measured the daily physical activity levels of ParkFit patients by using an ambulatory accelerometer.

The results of the ParkFit trial are described in Chapter 6. Primary aim of the trial is to investigate whether the ParkFit program leads to increased physical activity levels that persist for two years. Physical activity levels will be measured every six months using an interview-based 7-day recall. To investigate whether increased levels of activity might be beneficial for patients, physical fitness and quality of life are assessed, as well as the number of falls.



To further facilitate implementation of the ParkFit program into everyday clinical practice, we also evaluated the trial experience with the ParkFit program. These results are described in Chapter 7.

Finally, Chapter 8 summarizes this thesis and Chapter 9 discusses the main findings. Moreover, future challenges are described.

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CHAPTER

02

PHYSICAL INACTIVITY IN PARKINSON'S DISEASE JOURNAL OF NEUROLOGY 2011;258(12):2214-21.

Marlies van Nimwegen, Arlène D Speelman, Esther J M Hofman-van Rossum, Sebastiaan Overeem, Dorly J H Deeg, George F Borm, Marleen H L van der Horst, Bastiaan R Bloem, and Marten Munneke

02 ABSTRACT

02

physical inactivity in parkinson's disease

promotion of physical activity in parkinson's disease • the challenge to change behavior

INTRODUCTION

BACKGROUND

Patients with PD are likely to decrease their

pectedly, two studies found that patients and



Patients with Parkinson’s disease (PD) are likely to become physically inactive, because of their

daily physical activities, because of physi-

controls spent comparable amounts of time

motor, mental and emotional symptoms. However, specific studies on physical activity in PD are

cal impairments, fatigue and apathy. Such

being active 47 48.

scarce, and results are conflicting. Here, we quantified daily physical activities in a large cohort

a sedentary lifestyle is undesirable, because

The determinants of physical activity in PD

of PD patients and another large cohort of matched controls. Moreover, we investigated the

physical inactivity is a risk factor for cardio-

remain incompletely understood49. Generic

influence of disease-related factors on daily physical activities in PD patients.

vascular disease, diabetes mellitus, cognitive

factors such as age 50, gender50 51, and health

impairment, osteoporosis, and depression .

status 50 are associated with the level of physi-

METHODS

Moreover, physical inactivity may worsen var-

cal activity in healthy adults. Furthermore,



Daily physical activity-data of PD patients (n=699) were collected in the ParkinsonNet trial, and

ious non-motor symptoms, such as insomnia

depression is a risk factor for developing a sed-

of controls (n=1,959) in the Longitudinal Aging Study Amsterdam (LASA); data were determined

and constipation.

entary lifestyle52. Such factors may also affect

using the LAPAQ, a validated physical activity questionnaire. In addition, variables that may

Thus far, only a few studies examined physical

exercise behavior in patients with PD. Identify-

affect daily physical activities in PD were recorded, including motor symptoms, depression, disa-

activity in PD, and the results were inconsist-

ing the determinants of physical activity may

bility in daily life, and co-morbidity.

ent. Several studies found reduced levels of

help to structure new exercise interventions.

physical activity, but activity levels were not

Here, we quantified daily physical activities in

RESULTS

assessed optimally (either indirectly using

a large group of PD patients, and analyze the



Patients were physically less active; a reduction of 29% compared to controls (95% CI, 10-44%).

visual analogous scales 43, or using activity

associated determinants, using data from the

Multivariate regression analyses demonstrated that greater disease severity, gait impairment, and

monitors mounted at the wrist, rather than the

ParkinsonNet trial (699 patients)12

greater disability in daily living were associated with fewer daily physical activities in PD (R =24%).

leg ), or studies were very small

population-based LASA study (1,959 controls)53.

14

2

CONCLUSION

44

In this large study, we show that PD patients are about one third less active compared to con-

METHODS

trols. While disease severity, gait, and disability in daily living predicted part of the inactivity,

PARTICIPANTS

a portion of the variance remained unexplained, suggesting that additional determinants may

Patients

also affect daily physical activities in PD. Because physical inactivity has many adverse conse-



quences, work is needed to develop safe and enjoyable exercise programs for patients with PD.

45 46

. Unex-

13

and the

The ParkinsonNet trial was a cluster randomized trial involving 699 participants that evaluated community-based professional networks of physiotherapists (ParkinsonNet)12 13. Eligibility criteria for patients were: (a) PD according to the UK PDS Brain Bank criteria2; (b) living independently in the community; (c) 23; and (f) no severe co-morbidity interfering with daily functioning. Stage of the disease was scored according to the original Hoehn and Yahr (H&Y) stages 54. Most patients (81.6%) had moderate disease severity (i.e. H&Y 2-3) (Table 2.1). Mean age was 68.6 ± 7.7 years, 409 patients were men (58.5%), and average disease duration was 5.3 years. Full ethical approval has been granted for the study. All patients signed informed consent. In the study described here, we used baseline data.

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promotion of physical activity in parkinson's disease • the challenge to change behavior

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physical inactivity in parkinson's disease

TABLE 2.1

Controls Controls were derived from the Longitudinal Aging Study Amsterdam (LASA), a prospective

CHARACTERISTICS OF THE PARTICIPANTS

study of persons aged 55 to 85 years old (1995-1996) . This cohort forms a nationally repre53

Patients

sentative sample of the older Dutch population and thus creates a good control group. After exclusion of participants older than 80 years, data of 1,959 controls were available for the analyses. Mean age was 65.8 ± 7.0 years and 921 subjects were men (47.0%) (Table 2.1). Full ethical approval has been granted for the study and all respondents gave informed consent at the start of the study. Daily physical activities in patients and controls In both groups, daily physical activities were measured with the LASA Physical Activity Questionnaire (LAPAQ)55. The LAPAQ covers frequency and duration of different activities

Controls

Total population

Random sample

699

76

1959

Men

409 (58.5%)

44 (57.9%)

921 (47.0%)

Age

68.6 (± 7.7)

67.6 (± 8.2)

65.8 (± 7.0)

Time since diagnosis

5.3 (± 4.7)

3.9 (± 3.7)

N

Education level

during the previous two weeks55 56. Activities covered in the LAPAQ include: walking outside,

Low

385 (55.1%)

26 (34.2%)

1243 (63.5%)

cycling, gardening, light and heavy household activities, and a maximum of two sport activities.

Medium

112 (16.0%)

16 (21.1%)

367 (18.8%)

High

150 (21.5%)

25 (32.9%)

349 (17.8%)

52 (7.4%)

9 (11.8%)

0 (0.0%)

To consider different levels of intensity of activities, a metabolic equivalent value (MET) was assigned to each activity to calculate the number of kilocalories spent per day per kilogram of body weight57. In addition, types of different activities (‘inside’ and ‘outside the house’) were specified.

Missing

The LAPAQ was initially designed as an interview-based physical activity questionnaire; in the

Partner

LASA study, data was collected this way. A self-completed version was used in the ParkinsonNet

Yes

522 (74.7%)

54 (71.1%)

1451 (74.1%)

No

131 (18.6%)

13 (17.1%)

508 (25.9%)

46 (6.7%)

9 (11.8%)

0 (0.0%)

1

77 (11.0%)

7 (9.2%)

and motor section of the unified Parkinson’s Disease Rating Scale58), fear of falling (Falls Efficacy

2

327 (46.8%)

36 (47.4%)

Scale-International59), anxiety and depression (Hospital Anxiety and Depression Scale60), mo-

3

243 (34.8%)

25 (32.9%)

bility (timed up and go test61), freezing of gait (Freezing of Gait questionnaire62), walking speed

4

34 (4.9%)

7 (9.2%)

Missing

18 (2.6%)

1 (1.3%)

trial. To reduce recall bias, the time window was limited to one week. A random sample of the ParkinsonNet trial population (n=76) completed the questionnaire, and was also interviewed similar to the controls. The subgroup was comparable to the total PD population (Table 2.1).

Missing Hoehn & Yahr

DISEASE RELATED FACTORS ASSOCIATED WITH DAILY PHYSICAL ACTIVITIES IN PD In the ParkinsonNet trial, a wide range of variables was assessed: disease severity (H&Y stages

(6-meter walk test), disability in daily life (Self-assessment Parkinson's Disease Disability Scale63), co-morbidity (cumulative illness rating scale64), and “faller status” (≥ 1 fall in the preceding year). Patient characteristics included gender, age, education level and marital status. We stu-

Data are mean (SD) or number (%).

died the influence of these disease-related factors on daily physical activities. We classified six dimensions to analyze all factors: demographics (gender, age, education level, and marital status); health status/disease severity (H&Y, UPDRS, CIRS, and time since diagnosis); walking performance/mobility (TUG, FOGQ, and walking speed); fear of falling, anxiety and depression (HADS and FES-I); disability in daily life (SPDDS); and faller status.

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promotion of physical activity in parkinson's disease • the challenge to change behavior

ANALYSES

02

physical inactivity in parkinson's disease

FIGURE 2.1

Data of daily physical activities in both groups were summarized with medians and 25th and

LEVELS OF DAILY PHYSICAL ACTIVITIES PER HOEHN & YAHR STAGE (H&Y); THE ERROR BARS

75th percentiles. Since the LAPAQ scores were skewed, linear logarithmic transformation was

REFLECT THE 95% CONFIDENCE INTERVALS.

applied for all subsequent analyses. Differences between patients and controls in minutes per day as well as in kilocalories per day were evaluated using linear regression analyses, with adjustment for gender, age, education level and marital status. Furthermore, linear regression analysis with forward variable selection was performed to study the association between the dimensions mentioned above and daily physical activities. First, we used a stepwise selection procedure to identify additional variables that contributed significantly. In addition, we used a hierarchic approach whereby in each subsequent step of the selection procedure, an F-test was carried out for each dimension that was not yet in the model. First, the demographic variables were included in the model. The dimension with the smallest P value was then included, provided that it was statistically significant. The selection procedure was stopped when the F-test of none of the remaining dimensions was significant. A two-sided P value of less than 0.05 was considered to indicate statistical significance. In general, selection procedures provide a model, but they do not guarantee that the model is unique. Therefore, we evaluated whether the resulted model was optimal and unique by calculating the explained variance (R 2) for all possible alternative models.

RESULTS DAILY PHYSICAL ACTIVITIES IN PD COMPARED TO CONTROLS Patients spent 111 minutes per day (interquartile range 58 – 206) on daily physical activities, compared to 150 minutes for controls (interquartile range 89 – 232). This amount lead to a 29% reduction in patients versus controls (95% CI, 10 to 44%; p 3 times a week vigorous-

excluded because they were not willing to participate. Finally, 586 patients signed informed

intensity physical activity > 60 minutes; or > 3 times a week moderate-intensity physical activity > 150 minutes;

consent. The number of enrolled patients is less than the power calculation required. However,

*** Severe disease = H&Y > III; MMSE 98% of their day was

ommended level, what the range in physical

The primary aim of this study was to produce for

spent on sedentary to light-intensity activities. Eighty-two percent of the participants were ‘phy-

activity is across patients, and which factors

the first time a performance-based description of

sically inactive’ (0 days/week of 30-minute activity); 17% were ‘semi-active’ (1-4 days/week of

determine differences in daily physical activ-

daily physical activity in self-identified sedentary

30-minute activity). Age, gender, physical fitness, and scores on the Unified Parkinson’s Disease

ity across patients. This is important to know,

PD patients. Second, by comparing these results

Rating Scale explained 69% of the variability in daily physical activity.

because it could have implications for the

with criteria of the daily physical activity guide-

way physical activity levels can be enhanced.

line,121 we examined whether these patients were

CONCLUSION

A number of related factors have been sug-

really ‘physically inactive’ (in the sense of failing



29

19 82 117 118-120

Performance-based measurements confirmed that most self-identified sedentary PD patients are

gested in the literature to account for differ-

to meet the recommended level of physical activ-

‘physically inactive’. However, the variance in daily physical activity across subjects was conside-

ences, including disease-related features, 31 115

ity once a week) or ‘semi-active’ (in the sense of

rable. Higher age, being female, and lower physical capacity were the most important determi-

demographics, psychological characteristics

meeting the recommended level of physical activ-

nants of reduced daily physical activity. Future therapeutic interventions should aim to improve

and physical fitness.

ity one to four days per week).21 Third, we aimed

daily physical activity in these high-risk patients, focusing specifically on modifiable risk factors.

However, it remains unknown how these factors

32 115 124 125

to identify determinants of daily physical activity

specifically contribute to the variability in daily in these patients.

METHODS STUDY DESIGN

All subjects in the present study are participants in the ParkFit trial,42 and their baseline data were used here. The ParkFit trial is a multicenter, randomized controlled trial whose aim is to increase physical activity levels in sedentary PD patients.42 The study complied with principles outlined in the Declaration of Helsinki and was approved by the local ethics committee. All participants gave their written informed consent.

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quantifying daily physical activity and determinants in sedentary patients with parkinson's disease

promotion of physical activity in parkinson's disease • the challenge to change behavior

STUDY SAMPLE

as the length of time in which at least 70% of the subject sample was wearing the accelerometer.



Only the last seven consecutive valid days were included for data analysis.

The ParkFit trial recruited patients from 32 community hospitals between September 2008 and January 2010. All of these patients had received chronic care from a neurologist. Patients



Daily physical activity was expressed as mean total energy expenditure per day (in kcal), which

were included if they were diagnosed with idiopathic PD,2 were rated with a Hoehn and Yahr

was calculated by dividing the sum of energy expenditure (in kcal) of the last seven consecutive

(HY) stage ≤3,126 and were between 40 and 75 years of age. Also, to be included candidate

valid days by seven for each participant. This consisted of sedentary to light-intensity activities

subjects had to report that they do not meet the recommended level of daily physical activity

(0-3.5 kcal/minute), moderate-intensity activities (3.5-7 kcal/minute), and vigorous-intensity ac-

(i.e.,moderate-intensity physical activity for >150 minutes for >3 times/week or vigorous-inten-

tivities (>7 kcal/minute) per day.134

sity physical activity for >60 minutes for >3 times/week ). Included PD patients are referred to 15

throughout this study as being ‘self-identified sedentary’ to make it clear that their initial status



Psychological characteristics

was determined by perceived daily physical activity, not objectively measured activity. Exclusion



Depression and generic anxiety were measured with the Hospital Anxiety and Depression Scale

criteria concerned marked cognitive impairment (Mini-Mental State Examination [MMSE] score of 7 kcal/

validated for PD patients, no extensive problems with validity in this specific population were

minute).134 Patients were classified as ‘physically active’ if they were physically active for a mini-

expected. No unambiguous evidence exists to indicate that patients expend more energy than

mum of 30 minutes/day (in bouts of ≥ 10 minutes), if the intensity of the activity was moderate

healthy subjects to achieve the same movements, or that patients’ resting energy is elevated.46 130

or vigorous, and if they performed this activity for a minimum of 5 days/week. Patients were

Several literature-based decisions were made with regard to preprocessing the accelerometer

classified as ‘semi-active’ if they were moderately to vigorously active (30 min/day) for 1-4 days/

data.131 Patients were asked to wear the accelerometer every day for a period of two weeks, a ‘day’

week, and as ‘physically inactive’ if they were active for zero days/week. For exploratory reasons,

being 24 hours. ‘Non-wearing time’ was defined as a period of at least 60 consecutive minutes of

we calculated prevalence rates based on the total number of minutes of moderate- to vigorous-

zero’s, with a maximum of 2 minutes larger than 0.2 kcal.

intensity activities per day for ‘physically active’, ‘semi-active’ and ‘physically inactive’ patients.

67 132

Subtracting non-wearing time from

24-hours resulted in the ‘wearing time’. To determine the minimal wearing time per day acceptable for a valid measurement, we used the ‘70/80’ rule.

67 131 133

Average bout-length was assessed as well.

A measurement was deemed valid if the

patient wore the accelerometer for at least 80% of the ‘wearing day’. ‘Wearing day’ was defined

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quantifying daily physical activity and determinants in sedentary patients with parkinson's disease

promotion of physical activity in parkinson's disease • the challenge to change behavior

The first step for identifying determinants of daily physical activity was to calculate correlations

TABLE 5.1

(Spearman’s rho) between mean total energy expenditure and demographics, disease-specific

PATIENT CHARACTERISTICS

characteristics, physical fitness and psychological characteristics. The second step was to anaPatient characteristics (n=467)

lyze differences in mean total energy expenditure between men and women, HY stages, and

Demographic characteristics

education levels by using Mann-Whitney/Kruskall Wallis tests. The final step was to fit a linear

Age (years)

mixed-effects model by using maximum likelihood. All analyses were performed in the statistical programming language R and SPSS (17.0); p-values of 30)

Number (%)

108 (23%)

Yes

Number (%)

399 (86%)

No

Number (%)

67 (14%)

Low

Number (%)

272 (58%)

High

Number (%)

195 (42%)

Median (IQR)

44.0 (67.0)

Mean (SD)

61.8 (52.6)

Spouse

Of those excluded, 1263 did not qualify because they met or exceeded the physical activity guideline. Of the remaining 1687 eligible patients, 1101 were not willing to participate.42 In total 586 were randomized into the ParkFit trial. Of these, 119 patients (20%) were excluded

Education

from the present study based on accelerometry-data preprocess decisions (see Methods). In total, 467 patients (80%) had valid accelerometry measurements (≥659 minutes/day) on at least

Disease specific characteristics

seven consecutive days. There were no significant differences in age (Mann-Whitney U=26388;

Time since diagnosis (months)

p=.40); gender (Chi²=1.44; p=.23); body mass index (BMI) (Mann-Whitney U=27292; p=.76); HY stage (Chi²=1.82; p=.77); or disease duration (Mann-Whitney U= 27186; p=.72) between

Hoehn & Yahr stage

patients with insufficient (3 times a week vigorous-intensity physical activity > 60 minutes; or >3 times a week moderate-intensity physical activity > 150 minutes; ** Severe disease = H&Y > III; MMSE < 24; severe co-morbidity interfering with daily functioning; use of daily care in an institution; or deep brain stimulation

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promotion of physical activity in parkinson's disease • the challenge to change behavior

06

promotion of physical activity and fitness in sedentary patients with parkinson's disease

TABLE 6.2

TABLE 6.3

EFFECT OF THE INTERVENTION (IN HOURS PER WEEK) ON THE LEVEL OF PHYSICAL ACTIVITY MEASURED

EFFECT OF THE INTERVENTION ON THE SECONDARY OUTCOME MEASURES

WITH THE LASA PHYSICAL ACTIVITY QUESTIONNAIRE (LAPAQ) N LAPAQ

N

ParkFit

N

Controls

Estimated

ParkFit

N

Controls

Activity Diary

Baseline

299

12.8 (8.3-20.3)

287

13.8 (8.3-23.9)

Baseline (hrs per week)

297

5.5 (3.1-10.3)

282

6.3 (3.3-10.5)

6 months

285

13.2 (9.2-20.5)

277

14.2 (8.5-22.0)

Median 6 to 24 months

276

7.6 (4.7-12.4)

276

6.9 (4.2-10.8)

12 months

281

12.5 (7.2-21.1)

277

12.4 (7.3-17.9)

Mean change

275

1.3

273

0.5

18 months

277

12.3 (7.0-19.0)

271

12.3 (6.8-19.1)

24 months

273

12.5 (6.3-18.4)

267

12.0 (7.0-18.3)

Baseline (kcal per day)

273

453 (368-618)

269

462 (346-604)

Median 6 to 24 months

269

504 (390-667)

269

440 (355-582)

Mean change

254

38.7

258

-14.2

Baseline

297

26.0 (13.7)

286

26.2 (13.1)

Mean 6 to 24 months

278

26.4 (13.7)

277

27.7 (12.7)

Mean change

278

0.1

276

1.7

Baseline (distance in m)

298

391.6 (87.5)

283

392.9 (84.5)

Mean 12 and 24 months

256

404 (95.1)

256

394.4 (86.5)

Mean change

255

8.4

253

-1.6

Estimated difference (CI)*

p

difference (CI)*

p

difference (CI)*

Estimated

30% (17% to 45%)

67

38% (13% to 68%)*

-0.8 (-2.6 to 1.0)

17.0 (2.6 to 31.4)*

19% (3% to 37%)*

-0.8 (-2.2 to 0.6)

9.1 (-2.8 to 20.9)

40% (10% to 80%)*

-0.6 (-2.7 to 1.6)

12.0 (-4.4 to 28.4)

< 3.75

27% (5% to 54%)*

-1.4 (-3.0 to 0.3)

15.9 (2.7 to 29.0)*

patients with lower disease severity, shorter disease duration and elderly patients appeared to

> 3.75

23% (3% to 47%)*

0.13 (-1.6 to 1.9)

4.6 (-9.5 to 18.7)

benefit relatively most.

< 32

24% (3% to 51%)*

-1.7 (-3.4 to -0.05)*

15.0 (1.7 to 28.4)*

> 32

30% (9% to 55%)*

-0.2 (-1.9 to 1.6)

Men Women

DISCUSSION We aimed to evaluate the trial experience with the ParkFit program, as a basis to facilitate fu-

Gender##

Disease duration (years)

ture implementation into clinical practice. Both therapists and patients were positive about the intervention. Almost all therapists wished to use the ParkFit program in other patients, and 73% of patients would recommended the program to other patients. Subgroup analyses revealed that the program was effective in almost all subgroups. The most sedentary patients, women,

Disease severity (UPDRS III)

7.4 (-6.5 to 21.3)

The different elements of the ParkFit program were offered as a ‘total package’ to achieve a behavioral change. Since therapists were educated to offer this multifaceted program and we evaluated the program likewise, we cannot conclude whether specific elements were more or less effective. However, the results of the questionnaire gave some insight in the perceived suc-

Mobility (TUG, seconds) < 9.25

28% (7% to 52%)*

-1.2 (-2.8 to 0.4)

10.5 (-0.8 to 21.9)

> 9.25

21% (-0.1% to 46%)

-0.3 (-2.2 to 1.5)

9.3 (-6.0 to 24.6)

6

17% (-0.1% to 38%)

-1.3 (-2.9 to 0.3)

18.3 (5.5 to 31.0)*

Baseline physical activity (hours)

cess of the various components. Specifically, therapists reported education and the coaching sessions as main tools of the ParkFit program, while most patients reported the Activity Monitor as the most useful tool. Clearly, these three elements deserve optimal attention when delivering the ParkFit program in clinical practice. Future work is needed to decide which component is most effective in increasing physical activity levels, and if any component of the ParkFit program will also be effective when used in isolation.

Data reflect estimated differences and 95% confidence intervals; analyses were corrected for age, gender, H&Y,

The program had an excellent compliance: 85% of patients in the ParkFit program completed the

and baseline level; #without correction for age;

without correction for gender; *p < 0.05. Physical activity was

total intervention (van Nimwegen M and Speelman AD et. al, BMJ 2012, in press). Our results

measured with the LASA Physical Activity Questionnaire (LAPAQ); quality of life was measured with the Parkinson’s

concerning adherence are comparable with previous short-term programs (up to 6 months)168

Disease Questionnaire (PDQ-39); physical fitness was measured with the 6-minute walk test (6MWT). UPDRS III =

169

motor part of the Unified Parkinson’s Disease Rating Scale; TUG = Timed up and Go test.

an exercise program of six months aiming to reduce fall risk in PD, 54% of patients completed

##

but remarkably higher compared with previous long-term programs (up to 14 months).170 In

at least 75% of the sessions.169 Another study of group exercise in PD found an attendance rate of 73% during 14 months.170 Several aspects of our program could have contributed to its high

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promotion of physical activity in parkinson's disease • the challenge to change behavior

07

evaluation of implementation of the parkfit program

adherence. First, the individually tailored character of the intervention – with activities that par-

research should focus on the effects of ParkFit-like interventions in women, patients with lower

ticipants enjoyed – makes participation more palatable compared with exercise in general.165

disease severity and patients with a shorter disease duration.

Since patient and therapist jointly chose one or more (sport) activities, patients were allowed to follow their own wishes, adjusted to the individual situation. Second, the disease-specific



The ParkFit program was now offered solely by physiotherapists with PD-specific expertise, which

knowledge of the therapists could explain the high adherence. The intervention was delivered

likely helped to overcome any barriers imposed by the physical limitations. The question is

solely by experienced physiotherapists participating in the Dutch ParkinsonNet.13 ParkinsonNet

whether adding professionals from other disciplines might help to improve the quality of the

networks were specifically developed to improve the PD-specific expertise of health professio-

behavioral change program. One example that came from the interviews was a psychologist,

nals, and to increase patient volumes per therapists. Probably, due to these specific elements,

who could address the cognitive issues associated with PD, but who also adds specific expertise

therapists were able to adequately anticipate on perceived barriers of PD patients, and this

to change behavior. One could also consider adding sport instructors, since they have specific

could have improved patients’ adherence. Most patients who withdrew from the intervention

knowledge about coaching, counseling, sports and exercise. It will be interesting to examine the

did so just after baseline inclusion (4.7%). After about six months, another 5% of patients had

possible role of such sport instructors within the ParkFit program. For example, we anticipate

stopped with the program. Apparently, once patients participate and perceive no ‘starting’ pro-

that patients with greater disease severity will require more specific knowledge of a specialized

blems, there are hardly no reasons to stop with the intervention. This suggests that the program

physiotherapist, while patients in earlier stages could be coached solely by a sport instructor.

13

is feasible and achievable for patients. Besides the excellent compliance of patients, almost all involved therapists delivered the intervention for two years and completed both the interview and

CONCLUSION

the questionnaire. This shows great enthusiasm and interest with the ParkFit program.



Our analysis of the ParkFit program yielded several suggestions for improvement: 1) improve education for therapists with respect to theories about behavioral change; 2) formulate concrete and



Multivariate regression showed that larger changes in levels of physical activity were associated

specific examples of exercise goals; and 3) pay more specific attention to patients with co morbidi-

with less baseline physical activity. The major part of the explained variance was explained by

ties, cognitive dysfunction and a lack of motivation during education. Sedentary behavior is a major

baseline physical activity. This could be a simple regression to the mean effect, but it could also

public health problem, and physical activity can have various specific benefits for patients with PD.

suggest that poor daily participation in exercise is no reason to withhold patients a physical

We therefore recommend further implementation of this program into everyday clinical practice.

activity program such as ParkFit. Furthermore, better mobility was associated with greater increases in physical activity after two years. Moreover, therapists reported that patients without comorbidities and cognitive disturbances were more easy to stimulate towards an active lifestyle.

ACKNOWLEDGEMENTS

Therefore, physiotherapists should take poor baseline mobility, physical limitations, baseline



physical activity levels, and cognitive functioning of patients into account before starting a be-

We thank all patients and physiotherapists for participation. We would like to thank I. Boers, D. Drijkoningen, G. Kastenberg-van Spijker, and J. Tra for their contribution during data collection.

havioral change program, for example by engaging the immediate caregiver into the program.

Furthermore, we would like to thank T. Roordink, M. Gerrits and W. Trompers for their contribution.

Perhaps, patients should receive treatment (e.g. by increasing dopaminergic medication, or by



offering physiotherapy strategies such as cueing) prior to participation.



This study was primarily funded by ZonMw (The Netherlands Organization for Health Research and Development (75020012)) and The Michael J Fox Foundation for Parkinson’s research.



Subgroup analyses showed significant differences for almost all subgroups between patients in

Additional financial support was provided by VGZ (health insurance company); Glaxo Smith

the ParkFit program and controls. In the subgroups of women, patients with lower disease seve-

Kline; and National Parkinson Foundation.

rity and patients with a shorter disease duration, the benefits from the ParkFit program seem to greater. However, these results should be interpreted with caution, because the study was not set up to compare subgroups and had insufficient power to reliably detect differences. As such, the present results serve only as hypothesis-generating, which call for further confirmation in new studies. This work could focus on some promising hypotheses that came from our current research, suggesting that specific subgroups may benefit more than others. Specifically, further

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CHAPTER SUMMARY

08

promotion of physical activity in parkinson's disease • the challenge to change behavior

08

summary

CHAPTER 2 PHYSICAL INACTIVITY IN PARKINSON’S DISEASE Patients with Parkinson’s disease are widely presumed to follow a sedentary lifestyle, due to their physical, cognitive and emotional impairments. Nevertheless, only a few studies have thus far examined physical activity in PD, and the results were inconsistent. In Chapter 2, we provided new evidence to demonstrate the presence of physical inactivity in PD. Daily physical activity levels of patients with PD were compared with controls; data were obtained using a validated physical activity questionnaire (LASA Physical Activity Questionnaire (LAPAQ)). The results showed that patients were physically less active; a reduction of 29% in daily physical activities was found (95% CI, 10% to 44%). The loss of time spent on activities was most obvious in patients with greater disease severity. We also investigated the influence of disease-related factors on daily physical activities in patients with PD. Multivariate regression analyses demonstrated that greater disease severity, gait impairment, and greater disability in daily living were associated with daily physical activities in PD (R 2=24%). Patients with PD are less active compared with controls. This reduction is in part related to greater disease severity, more severe gait impairment, and greater disabilities in daily living.

CHAPTER 3 DESIGN AND INTERVENTION OF A RANDOMIZED CONTROLLED TRIAL TO PROMOTE PHYSICAL ACTIVITY IN PATIENTS WITH PARKINSON’S DISEASE Participating in regular physical activity reduces the risk of chronic diseases such as cardiovascular diseases, type 2 diabetes mellitus, osteoporosis and obesity. Moreover, promotion of physical activities may beneficially affect the clinical presentation of PD, and perhaps even modify the course of PD. However, changing a sedentary lifestyle is difficult; to increase physical activity in old persons or in patients with a chronic disease may be even harder. We developed a multifaceted intervention to promote physical activity in sedentary patients with PD (the ParkFit program). We designed a multicentre, randomized controlled trial comparing the ParkFit program with a matched general physiotherapy intervention. The ParkFit intervention program was based on theories and models of behavioral change and on widely used behavioral change techniques with proven effectiveness. Important elements of the program were: (a) the physiotherapist as activity coach who guided each individual patient towards a more active lifestyle during monthly personal coaching sessions; (b) a brochure with

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promotion of physical activity in parkinson's disease • the challenge to change behavior

education about the benefits of physical activity and suitable activities for PD patients; (c) identifying and overcoming any perceived barriers to engage in physical activity; (d) systematic goal setting, using a health contract and logbook; (e) stimulating patients to participate in group

08

summary

CHAPTER 5 QUANTIFYING LEVELS OF INACTIVITY IN PARKINSON’S DISEASE PATIENTS AND ITS DETERMINANTS

exercises to experience social support from peers; and (f) an ambulatory monitor with automa-

Questionnaires are widely used to measure daily physical activity in large populations. However,

ted feedback. Chapter 3 described the ParkFit program and the design of this large randomized

due to their subjective character, they might result in an under- or overestimation of the per-

controlled trial. The primary outcome of the trial was the change in physical activity over the

formed physical activities. The ParkFit study intended to include sedentary patients, based on a

course of two years measured with the LAPAQ, an interview-based 7-day recall. The trial would

physical activity screening questionnaire. It was not clear whether these self-reported sedentary

also search for possible health benefits and risks of increased physical activity in PD.

patients also had objective evidence for a sedentary lifestyle, as determined using quantitative accelerometry measurements. The aim of this study was to objectively assess physical activity

The ParkFit trial evaluates a new, multifaceted intervention program to achieve an enduring

behavior of all sedentary participants of the ParkFit study. Physical activity behavior was measu-

increase in physical activity specifically in patients with PD. The intervention is based on motiva-

red over seven days using a linear triaxial accelerometer which was worn as a necklace, on the

tional and behavioral change models, which are employed for the first time in patients with PD.

belt or in the pocket. Determinants of daily physical activity were additionally identified. In total, 467 patients (80%) had valid accelerometry measurements on at least seven consecutive

CHAPTER 4 MULTIVARIABLE ANALYSES OFTEN HAVE MULTIPLE SOLUTIONS; AN EXAMPLE

days.133 Median total energy expenditure was 464 kilocalories per day and participants spent 12 minutes per day on moderate or vigorous intensive activities. Consequently, none (except for one) of the participants met the recommendations for healthy physical activity (i.e. moderate-intensity cardio respiratory exercise training for at least 30 minutes per day for at least five days a week, which should

When we used forward variable selection to identify factors that were related to the level of phy-

take place in bouts of at least 10 minutes).15 Higher age, female gender, less physical fitness and

sical activity in Parkinson’s disease patients (Chapter 2), we found a model with four variables.

greater motor problems were related to less daily physical activity (R2=0.69; p